Structural Considerations in Affinity Maturation of Antibody-Based Biotherapeutic Candidates

Affinity maturation is an important stage in biologic drug discovery as is the natural process of generating an immune response inside the human body. In this chapter, we describe in silico approaches to affinity maturation via a worked example. Both advantages and limitations of the computational methods used are critically examined. Furthermore, construction of affinity maturation libraries and how their outputs might be implemented in an experimental setting are also described. It should be noted that structure-based design of biologic drugs is an emerging field and the tools currently available require further development. Furthermore, there are no standardized structure-based strategies yet for antibody affinity maturation as this research relies heavily on scientific logic as well as creative intuition.